Involvement of Alpha-Adrenergic Mechanisms in Growth Hormone Release Induced by Opioid Peptides in Conscious Rats

Abstract

The effects of synthetic enkephalin analog (FK 33–824) and β-endorphin on growth hormone (GH) secretion and their interaction with brain monoamines were investigated in unanesthetized male rats. Blood samples (0.4 ml each) were withdrawn every 10–20 min for 6 h from a catheter chronically implanted in the right atrium. In all control rats, immunoreactive GH secretion was pulsatile in nature and two major GH bursts were found to occur around 12.00 and 15.30.The opioid peptides were injected between bursts at 14.00. Following an intravenous administration of FK 33–824 (10 μg/100 g b.w.), there was an abrupt increase in plasma GH, which was significantly suppressed by naloxone (125 μg/ 100 g b.w., i.v.), a specific opiate antagonist. Pretreatment with reserpine (1 mg/100 g b.w., i.p.) abolished not only the natural GH burst but also the GH response to FK 33–824. Pretreatment with dopamine-β-hydroxylase inhibitors, diethyldithiocarbamate (DDC, 100 mg/100 g b.w., i.v.) and fusarate (10 mg/100 g b.w., i.v.) also inhibited the natural GH burst and GH rise induced by FK 33–824. Intravenous injection of clonidine (15 μg/100 g b.w.), an α-adrenergic stimulant, resulted in an increase in plasma GH in the rats pretreated with reserpine, DDC or fusarate. Phenoxybenzamine (1 mg/100g b.w., i.v.), an α-adrenergic blocking agent, inhibited the GH response to FK 33–824. On the other hand, GH release induced by FK 33–824 was not influenced by propranolol (1 mg/100 g b.w., i.v.), a β-adrenergic blocking agent, nor pimozide (0.1 mg/100g b.w., i.v.), a dopamine antagonist. Intraventricular administration of β-endorphin (5 μg/rat) also increased the plasma GH levels which were lowered by phenoxybenzamine. These findings suggest that α-adrenergic mechanisms are involved in GH release induced by opioid peptides in the rat.

Decreased hypothalamic growth hormone-releasing hormone content and pituitary responsiveness in hypothyroidism.

“…The use ofa combined in vivo/in vitro experimental design permitted the examination of individual components of this regulatory system in the same animals and also allowed an assessment of the relative importance of each in the overall impairment of GH secretion. GH secretion in the conscious rat is pulsatile with secretory bursts occurring regularly at 3-4-h intervals (17,27). The effect of thyroidectomy on spontaneous GH secretion was profound in that virtually no ultradian secretory episodes were detectable and most plasma GH levels were at or beneath the limit of detection ofthe assay.…”

“…The animals were housed for at least 4 wk after arrival in an environmentally controlled room (lights on: 0600-1800 h, temperature: 23±1 'C), with water and food provided ad libitum. Intravenous cannulae were then implanted into the right atrium as previously described (17). After cannulation, animals were caged individually, handled and weighed daily by the same investigator, and adapted to specific blood sampling procedures (18).…”

“…On the seventh day, the animals were injected with human GRH1-40)-OH (hGRH), 1 ug/l00 g, (kindly provided by Dr. J. Rivier, Salk Institute, San Diego, CA) at 1100 h when plasma GH concentrations were expected to be at trough levels (17)(18)(19) and the blood sampling procedure was repeated. hGRH was dissolved in acidified saline (pH 4.0) containing 1% albumin at a concentration of 10 ug/ml just prior to injection through the indwelling cannula.…”

Middle-Age Alterations in the Sexually Dimorphic Plasma Growth Hormone Profiles: Involvement of Growth Hormone-Releasing Factor and Effects on Cytochrome P450 Expression

“…Seven to ten days after serial blood collections for the determination of circulating growth hormone profiles, 3-and 12-month-old vehicle-treated and 12-month-old MSG-treated rats were administered the dopamine-␤-hydroxylase inhibitor sodium diethyldithiocarbamate trihydrate (DDC; Aldrich Chemical Co., Inc., Milwaukee, WI), which has been reported to block norepinephrine synthesis and GRF-dependent growth hormone secretion for up to 12 h (Negro-Vilar et al, 1979;Katakami et al, 1981;McCormick et al, 1985). The drug, dissolved in 0.9% NaCl at a dose of 500 mg/kg b.wt.…”

Intrahypothalamic Mu‐, not Delta‐ or Kappa‐Opioid Receptor Activation Causes Growth Hormone Secretion

“…Anatomical studies would also support a possible action of opioids at this site. Agents tested by this route include dynorphin (19), and synthetic derivatives of enkephalin (13,14,19). Of these, a muagonist ([D-Ala,MePhe.Met(O)-ollenkephalin) (1 3, 14) and mixed delta-and mu-agonists (D-Ala-Leu-enkephalin, D-Ala-Met-enkephalin) (19) increased G H levels suggesting that mu-receptors on median eminence terminals when activated also increase GHreleasing activity in the portal circulation.…”